Modified compound of andrographolide

Abstract

The present disclosure discloses a modified compound of andrographolide, and particularly discloses a compound shown in formula (I) and (II) or a pharmaceutically acceptable salt thereof.

What is claimed is: 
     
       1. A compound represented by formula (I), pharmaceutically acceptable salt or tautomer thereof, 
       
         
           
           
               
               
           
         
         wherein, 
         W is O, N(R 5 ) or a ring 
       
       
         
           
           
               
               
           
         
         R 5  is H, or a C 1-3  alkyl optionally substituted by 1, 2 or 3 halogen, OH, NH 2 , COOH, NHMe or N(Me) 2 ; 
         L 1  is selected from a single bond and —(CRR) 1-3 —; 
         R 1  is piperidinyl, which is optionally substituted with 1, 2, or 3 R or R′; 
         R 2 , R 3  are each independently selected from H, or are each independently selected from the group consisting of a C 1-6  alkyl, a C 1-6  heteroalkyl, and a C 3-6  cycloalkyl, which are optionally substituted with 1, 2, or 3 R or R′; 
         the ring A is 
       
       
         
           
           
               
               
           
         
       
       which is optionally substituted with 1, 2 or 3 R′;
 R is independently selected from F, Cl, Br, I, OH, NH 2 , CN, C(═O)OH, or from the group consisting of a C 1-6  alkyl, a C 1-6  heteroalkyl, and a -L-C 3-6  cycloalkyl, which is optionally substituted with 1, 2 or 3 R′; 
 L is a single bond, —O—, —S—, —C(═O)NH—, —NH—, —C(═O)O—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O) 2 ; 
 R′ is independently selected from halogen, CN, OH, N(CH 3 ) 2 , NH(CH 3 ), NH 2 , CHO, C(═O)OH, C(═O)NH 2 , S(═O)NH 2 , S(═O) 2 NH 2 , trihalomethyl, dihalomethyl, monohalomethyl, aminomethyl, hydroxymethyl, methyl, methoxy, formyl, methoxycarbonyl, Boc, methylsulfonyl, methylsulfinyl, ethyl, n-propyl, isopropyl, and C 3-6  membered cycloalkyl; 
 “hetero” refers to a heteroatom or a heteroatomic group selected from the group consisting of —C(═O)N(R)—, —N(R)—, —C(═NR)—, —S(═O) 2 N(R)—, —S(═O)N(R)—, —O—, —S—, ═O, ═S, —C(═O)O—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O) 2 — and —N(R)C(═O)N(R)—; 
 in any of the above cases, the number of heteroatom or heteroatom group is independently selected from 1, 2 or 3. 
 
     
     
       2. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , wherein R′ is each independently selected from the group consisting of F, Cl, Br, I, OH, NH 2 , CN, Me, CF 3 q, Et, N(CH 3 ) 2 , C(═O)OH, and Boc. 
     
     
       3. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , wherein R is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , CN and C(═O)OH, or is selected from the group consisting of Me, Et, OMe, OEt, 
       
         
           
           
               
               
           
         
       
       which is optionally substituted with 1, 2 or 3 R′. 
     
     
       4. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , wherein R 5  is selected from H, 
       
         
           
           
               
               
           
         
       
     
     
       5. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , wherein L 1  is selected from a single bond and a methylene. 
     
     
       6. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , wherein R 1  is 
       
         
           
           
               
               
           
         
       
       which is optionally substituted with 1, 2 or 3 R. 
     
     
       7. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , wherein R 2  and R 3  are independently selected from H, or independently selected from the group consisting of Me, Et, n-propyl, 
       
         
           
           
               
               
           
         
       
     
     
       8. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , which is selected from the group consisting of 
       
         
           
           
               
               
           
         
         wherein L 1 , R 1 , R 2 , R 3 , R 5 , and the ring A are as defined in  claim 1 . 
       
     
     
       9. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , which is selected from the group consisting of 
       
         
           
           
               
               
           
         
         wherein L 1 , R 1 , R 2 , R 5  and the ring A are as defined in  claim 1 . 
       
     
     
       10. The compound according to  claim 1 , which is selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       11. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , wherein R is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , CN, C(═O)OH, Me, Et, OMe, 
       
         
           
           
               
               
           
         
       
     
     
       12. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , wherein R 1  selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
       13. The compound, pharmaceutically acceptable salt or tautomer thereof according to  claim 1 , wherein R 2  and R 3  are independently selected from H, Me, Et,